Acute retinal necrosis

From EyeWiki
Original article contributed by: Lauren Taney, MD
All contributors: Dylan Griffiths, Lauren Taney, MD, Vinay A. Shah M.D. and WikiWorks Team
Assigned editor: Omesh P. Gupta, MD, MBA
Review: Assigned status Update Pending by Vinay A. Shah M.D. on December 6, 2014.
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Acute retinal necrosis (ARN) falls within the realm of necrotizing retinitis; it is an inflammatory condition that primarily affects the posterior pole. It typically features posterior uveitis and retinitis, inflammatory conditions believed to be caused by viruses within the herpes family. The principal viral agents are believed to be Varicella Zoster Virus (VZV) as well as Herpes Simplex Virus (HSV-1 and HSV-2), and, in much rarer cases, Cytomegalovirus (CMV) and Epstein Barr Virus (EBV).


Disease Entity[edit | edit source]

History[edit | edit source]

ARN was initially described by Urayama and colleagues in Japan in 1971.


Etiology[edit | edit source]

ARN is believed to result from the combination of retinal infiltration and occlusive arteriolitis in the setting of, most commonly, HSV or VZV infection. Serious visual loss may occur as a result of later retinal detachment or, much more rarely, optic neuropathy.


Risk factors[edit | edit source]

Genetics may play some role in an individual’s risk for ARN:

HLA-DQw7, HLA-Bw62, and HLA-DR4 in American Caucasians

HLA-Aw33, HLA-B44, and HLA-DRw6 in Japanese population


Epidemiology[edit | edit source]


This clinical entity is uncommon in the pediatric population but rather tends to affect adults in their fifth to seventh decades. A clear gender predilection has not been consistently demonstrated. Unlike other forms of infectious retinitis, immunocompetent patients tend to be more affected than immunosuppressed patients.


General pathology[edit | edit source]


There appear to be two distinct disease phases:

(1) acute herpetic phase, in which inflammation of the retina, retinal arteries, and choroidal vasculature occurs

(2) late cicatricial phase, in which retinal holes and tears commonly leading to subsequent retinal detachment occur


Pathophysiology[edit | edit source]


Acute phase: Viral particles in the retina and the vitreous provoke an intense inflammatory response. Retinal opacification corresponds with infiltration of the retina with viral particles and mononuclear cells. Lymphocytes and plasma cells, which produce antibodies to the provocative viral agent, likewise permeate the vitreous. Additionally, characteristic inflammation of the retinal arterioles occurs, resulting in vaso-occlusion and necrosis of dependent, downstream retinal tissue. Choroidal vasculature may also be beset by similar inflammatory changes.

Cicatricial phase: Organizational changes in the vitreous are thought to be the result of previous cellular infiltration during the acute phase. Contractile membranes may form in the vitreous and on the surface of the thinned, necrotic retina. Approximately 50% of patients will develop retinal detachments in the affected eye after ARN; the majority of retinal detachments occur within 3 months of the onset of ARN.


Primary prevention[edit | edit source]


The use of antiviral agents reduces the duration of the active phase of ARN and may thereby potentially minimize the duration and extent of retinal necrosis. Chronic use of antivirals after resolution of the active phase of ARN in one eye has also been shown to reduce the incidence of ARN in the fellow eye.

Prevention of the late visual sequelae of acute retinal necrosis, namely that of retinal detachment, may be partially reduced through prophylactic laser photocoagulation of the retina.


Diagnosis[edit | edit source]

History

Viral particles were originally identified, using electron microscopy, in the retina of those enucleated eyes with ARN.


Signs and symptoms

Patients with ARN typically present with acute onset of vision loss in one eye, which may be associated with redness, photophobia, pain, floaters, and flashes. Two-thirds of cases present with unilateral involvement.


Physical examination

Anterior segment involvement may include episcleritis, scleritis, corneal edema, keratic precipitates, and anterior chamber inflammation. Classically, posterior segment involvement includes vitreous inflammation, retinal vascular arteriolitis, and peripheral retinitis. Retinitis typically begins as multifocal areas of retinal yellowing and opacification, oftentimes with scalloped edges; initially, this patchy retinitis usually appears peripherally and, with progression, becomes increasing confluent and more posterior in its location.


Clinical diagnosis

The American Uveitis Society established the following as diagnostic criteria: (1) One or more foci of retinal necrosis with discrete borders, located in the peripheral retina (2) Rapid progression in absence of antiviral therapy (3) Circumferential spread (4) Occlusive vasculopathy, affecting arterioles (5) Prominent vitritis and/or anterior chamber inflammation


Diagnostic procedures

The diagnosis of ARN is usually made based upon clinical characteristics. However, in certain cases, it may be appropriate to analyze an aqueous or vitreous sample. In very rare examples, diagnostic vitrectomy or endoretinal biopsy may be necessary.


Lab tests

The following tests may be performed on aqueous or vitreous samples for further diagnostic certainty:

-viral culture

-use of direct or indirect immunofluorescence to identify viral antigens

-measurement of viral antibodies

-intraocular antibody titers with calculation of the Goldmann-Witmer coefficient

-PCR

Serologic testing may also aid in diagnosis.


Differential diagnosis

Progressive outer retinal necrosis (PORN)

CMV retinitis

Toxoplasma chorioretinitis

Syphilis

Lymphoma

Leukemia

Endophthalmitis

Behcet disease

Sarcoidosis

Sympathetic ophthalmia/VKH


Management[edit | edit source]

General treatment

Without intervention, the active phase of the disease can last between 6-12 weeks, while treatment with antivirals and/or steroids may reduce the latency to 4-6 weeks. Treatment modalities may include antiviral, anti-inflammatory, and antithrombotic therapy as well as retinal detachment prophylaxis.


Medical therapy

Antiviral therapy can be administered systemically (intravenously or by mouth) as well as through intravitreal injection. Prior to the mid-1990’s, antiviral agents were traditionally administered intravenously for at least the first week after diagnosis of ARN because it was believed that higher serum and intraocular concentrations of the antiviral agent could be achieved through IV administration; thereafter, it was considered appropriate to transition the patient to PO antivirals (acyclovir, famciclovir, valacyclovir, or valganciclovir) for an additional 4-12 weeks. Since the advent of newer antiviral agents, many physicians advocate using oral antiviralagents such as famciclovir, valacyclovir or valganciclovir as initial induction agents for treatment of ARN as well. Intravitreal delivery of antiviral agents is also used by many. Steroids and aspirin may also be appropriate for treatment.


Commonly used systemic antiviral agents include:

• Acyclovir

• Famciclovir

• Valacyclovir

• Ganciclovir

• Valganciclovir


Antiviral agents administered intravitreally may include:

• Ganciclovir (200-2000 ug per 0.1 mL)

• Foscarnet (1.2-2.4 mg per 0.1 mL)


Steroids may have a beneficial therapeutic effects if initiated 24-48 hours after the start of IV antiviral therapy or once regression of retinal necrosis been demonstrated:

• Prednisone 0.5-2.0 mg/kg/day by mouth for up to 6-8 weeks


Aspirin may minimize vascular thrombosis and propagation of further retinal ischemia and necrosis.


Topical steroid drops have also been shown to be beneficial, depending upon the degree of anterior segment inflammation.


Topical antiviral therapy has been shown not to be efficacious in treatment of ARN.


Medical follow-up

Patients with unilateral ARN should be closely followed with dilated examination of both of their eyes. Approximately 50% of patients with ARN will go on to develop a retinal detachment. Reports of second eye involvement range from 3-35%, with variable involvement attributable to etiologic agent, course of therapy, and immune status.


Surgery

Some retina specialists advocate the use of prophylactic laser along the posterior margin of the junction of necrotic and non-necrotic retina to prevent incidence of retinal detachment. The rates of success in preventing retinal detachment are variable, and consensus does not exist on whether laser demarcation should be employed.

Vitrectomy with or without use of scleral buckle, with use of either gas or silicone oil, is reserved for those cases in which retinal detachment occurs.


Complications

Retinal holes and tears

Retinal detachment

Proliferative vitreoretinopathy

Vitreous hemorrhage

Macular pucker

Optic neuropathy

Encephalitis


Prognosis[edit | edit source]

The visual outcome on those eyes affected by ARN is variable and largely depends upon vision at time of presentatation as well as whether or not a retinal detachment occurs secondarily. Whether or not a retinal detachment occurs may, in turn, depend upon the extent of retinal necrosis on diagnosis, the amount of vitritis overlying areas of retinal necrosis (with more vitritis associated with a higher risk of RD), and varying response to treatment regimens.


References

Agarwal, A. “Acute retinal necrosis.” Gass’ Atlas of Macular Diseases, Fifth Edition, London: Elsevier, 2012, 900-907.

Aizman A, Johnson M, Elner S. Treatment of Acute Retinal Necrosis Syndrome with Oral Antiviral Medications. Ophthalmology 2007, 114: 307–312.

Aslanides IM, De Souza S, Wong DT, et al. Oral valacyclovir in the treatment of acute retinal necrosis syndrome. Retina
2002, 22: 352–354.

Blumenkranz MS, Culbertson WW, Clarkson JG, et al.  Treatment of the acute retinal necrosis syndrome with intravenous
acyclovir. Ophthalmology 1986, 93: 296–300.

Culbertson WW, Blumenkrantz MS, Haines H, et al. The acute retinal necrosis syndrome. Part 2: histopathology and
etiology. Ophthalmology 1982, 89:1317–1325.

Duker JS, Blumenkranz MS. Diagnosis and management of the acute retinal necrosis (ARN) syndrome. Surv Ophthalmol
1991, 35: 327–343.

Emerson GG, Smith JR, Wilson DJ, et al. Primary treatment of
acute retinal necrosis with oral antiviral therapy. Ophthalmology
2006, 113: 2259–2261.

Ezra E, Pearson RV, Etchells DE, et al. Delayed fellow eye involvement in acute retinal necrosis syndrome. Am J
Ophthalmol 1995, 120:115–117.

Figueroa MS, Garabito I, Gutierrez C, Fortun J. Famciclovir for the treatment of acute retinal necrosis (ARN) syndrome.
Am J Ophthalmol 1997,123: 255–257.

Lau C, Missotten T, et al. Acute Retinal Necrosis. Ophthalmology 2007, 114: 756–762.

Luu KK, Scott IU, Chaudhry NA, et al. Intravitreal antiviral injections as adjunctive therapy in the management of immunocompetent
patients with necrotizing herpetic retinopathy. Am J Ophthalmol 2000, 129: 811–813.

Palay DA, Sternberg P, Jr., Davis J, et al. Decrease in the risk of bilateral acute retinal necrosis by acyclovir therapy. Am J
Ophthalmol 1991, 112: 250 –255.

Tibbetts M, Shah C, et al. Treatment of Acute Retinal Necrosis. Ophthalmology 2010, 117: 818–824.

Vemulakonda G, Pepose J, Van Gelder R. “Acute Retinal Necrosis Syndrome.” Retina, Fifth Edition, London: Elsevier, 2013, 1523-1531.